Severe HBV-Associated Hepatitis in Infants from the Same Family: Two Clinical Cases with Different Outcomes

Acute hepatitis B virus (HBV) infection is rare during infancy, and severe symptomatic HBV-associated hepatitis is even less common. We describe two siblings who developed severe HBV-associated liver injury during infancy, two years apart, but experienced markedly divergent clinical outcomes. Clinical, laboratory, virological, microbiological, imaging, therapeutic, and follow-up data were retrospectively reviewed. Household members were subsequently tested for HBV and HDV. The first infant, a 5-month-old girl, presented with HBsAg positivity, negative serological markers for HAV, HCV, and HEV, and severe acute liver injury with a fulminant clinical course that resulted in death. Because anti-HBc IgM, HBV DNA, repeat HBsAg testing, and follow-up serology were unavailable, acute HBV infection could not be confirmed, and the episode was therefore classified as presumed HBV-associated fulminant hepatitis. The rapidly fatal clinical course precluded a comprehensive etiological evaluation, and the available medical records did not fully document the diagnostic work-up. The second patient, a 4-month-old boy, presented with serological and molecular evidence of acute HBV infection, including low-level HBV DNA, total anti-HDV positivity of uncertain clinical significance, and positive CMV IgM/IgG serology. He also had a urinary tract infection (UTI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Without HDV RNA and CMV DNA testing, active HDV infection and clinically significant CMV disease could not be definitively confirmed, while passive transfer of maternal anti-HDV antibodies could not be excluded. The patient required prolonged hospitalization, during which he received supportive, replacement, and antimicrobial therapy. He recovered, and long-term follow-up demonstrated HBsAg clearance with undetectable HBV DNA. Testing of household members revealed chronic HBV infection in the mother and maternal grandmother, both of whom had detectable HDV RNA, consistent with ongoing HBV/HDV circulation within the family. However, without viral sequence data from the infants, the source, route, timing, and direction of transmission could not be established. These cases illustrate the potential severity of HBV-associated hepatitis during infancy and its highly variable clinical outcomes. They also underscore the importance of antenatal HBV screening, timely immunoprophylaxis, and cautious interpretation of suspected viral coinfections when molecular confirmation is unavailable.